methyl 2-isothiocyanatobenzoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 2-isothiocyanatobenzoate (6.0 g, prepared as described in J. Org. Chem., 1962, 27, 3701) and N,N-dimethylhydrazine (6 ml) in ethanol (60 ml) was stirred at room temperature for 1 hour. The precipitate was filtered off and dried to give methyl 2(3'-dimethylaminothioureido)benzoate (6.73 g, m.p. 149°-152°). The precipitate was filtered off dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 10.9 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine in 150 parts of tetrahydrofuran was added dropwise a solution of 6 parts of methyl 2-isothiocyanatobenzoate in 30 parts of tetrahydrofuran at room temperature: slightly exothermic reaction, the temperature rose to 30° C. Upon completion, stirring at room temperature was continued for one hour. The reaction mixture was evaporated. The residue was stirred in trichloromethane. The formed precipitate was filtered off and crystallized from 2-propanone. The product was filtered off and dried, yielding 5.2 parts of 3-[2-[4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl]ethyl]-1,2-dihydro-2-thioxo-4(3H)-quinazolinone; mp. 198.5° C. (compound 131). slightly exothermic reaction rose to 30° C The reaction mixture was evaporated The residue was stirred in trichloromethane The formed precipitate was filtered off crystallized from 2-propanone The product was filtered off dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 10.9 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine in 150 parts of tetrahydrofuran was added dropwise a solution of 6 parts of methyl 2-isothiocyanatobenzoate in 30 parts of tetrahydrofuran at room temperature: slightly exothermic reaction, the temperature rose to 30° C. Upon completion, stirring at room temperature was continued for one hour. The reaction mixture was evaporated. The residue was stirred in trichloromethane. The formed precipitate was filtered off and crystallized from 2-propanone. The product was filtered off and dried, yielding 5.2 parts of 3-[2-[4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl]ethyl]-1,2-dihydro-2-thioxo-4(3H)-quinazolinone; mp. 198.5° C. (compound 131). slightly exothermic reaction rose to 30° C The reaction mixture was evaporated The residue was stirred in trichloromethane The formed precipitate was filtered off crystallized from 2-propanone The product was filtered off dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1H-benzo[d]imidazol-5-amine (0.14 g, 1.08 mmol) and methyl 2-isothiocyanatobenzoate (0.21 g, 1.08 mmol) were dissolved ind 10 mL of THF. The mixture was stirred by heating under reflux over night. The resulted insoluble solid was separated by suction through a frit and washed with THF to give a white solid. by heating under reflux over night The resulted insoluble solid was separated by suction through a frit washed with THF to give a white solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1H-benzo[d]imidazol-5-amine (0.14 g, 1.08 mmol) and methyl 2-isothiocyanatobenzoate (0.21 g, 1.08 mmol) were dissolved ind 10 mL of THF. The mixture was stirred by heating under reflux over night. The resulted insoluble solid was separated by suction through a frit and washed with THF to give a white solid. by heating under reflux over night The resulted insoluble solid was separated by suction through a frit washed with THF to give a white solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound was synthesized starting from methyl 2-isothiocyanatobenzoate (0.773 g, 4.0 mmol) and 3-(1H-imidazol-1-yl)propan-1-amine (9) (0.5 g, 4.0 mmol) as described above. The compound was synthesized

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound was synthesized starting from methyl 2-isothiocyanatobenzoate (0.093 g. 0.48 mmol) and 3-(4-methyl-1H-imidazol-1-yl)propan-1-amine (9) (0.067 g, 0.48 mmol) as described above. The compound was synthesized

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound was synthesized starting from methyl 2-isothiocyanatobenzoate (0.276 g, 1.43 mmol) and 3-(5-methyl-1H-imidazol-1-yl)propan-1-amine (5) (0.198 g, 1.43 mmol) as described above. The compound was synthesized

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Isothiocyanato-benzoic acid methyl ester (0.58 mL, 3.69 mmol) was added to a solution of 2-isopropyl aniline (500 mg, 3.69 mmol) and sodium methoxide (10 mg) in 2-propanol (10 mL) at room temperature and heated at reflux for 16 hr. The reaction mixture was concentrated to dryness under vacuum. The crude material was washed with dichloromethane (2×10 mL), 10% methanol in chloroform (2×10 mL) and dried under reduced pressure to afford 3-(2-isopropyl-phenyl)-2-mercapto-3H-quinazolin-4-one (600 mg, 55%) as white solid. heated at reflux for 16 hr The reaction mixture was concentrated to dryness under vacuum The crude material was washed with dichloromethane (2×10 mL), 10% methanol in chloroform (2×10 mL) dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Isothiocyanato-benzoic acid methyl ester (0.58 mL, 3.69 mmol) was added to a solution of 2-isopropyl aniline (500 mg, 3.69 mmol) and sodium methoxide (10 mg) in 2-propanol (10 mL) at room temperature and heated at reflux for 16 hr. The reaction mixture was concentrated to dryness under vacuum. The crude material was washed with dichloromethane (2×10 mL), 10% methanol in chloroform (2×10 mL) and dried under reduced pressure to afford 3-(2-isopropyl-phenyl)-2-mercapto-3H-quinazolin-4-one (600 mg, 55%) as white solid. heated at reflux for 16 hr The reaction mixture was concentrated to dryness under vacuum The crude material was washed with dichloromethane (2×10 mL), 10% methanol in chloroform (2×10 mL) dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 10.9 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine in 150 parts of tetrahydrofuran was added dropwise a solution of 6 parts of methyl 2-isothiocyanatobenzoate in 30 parts of tetrahydrofuran at room temperature: slightly exothermic reaction, the temperature rose to 30° C. Upon completion, stirring at room temperature was continued for one hour. The reaction mixture was evaporated. The residue was stirred in trichloromethane. The formed precipitate was filtered off and crystallized from 2 -propanone. The product was filtered off and dried, yielding 5.2 parts of 3-[2-[4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl]ethyl]-1,2-dihydro-2-thioxo-4(3H)-quinazolinone; mp. 198.5° C. (compound 131) slightly exothermic reaction rose to 30° C The reaction mixture was evaporated The residue was stirred in trichloromethane The formed precipitate was filtered off crystallized from 2 -propanone The product was filtered off dried